Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension

Christopher R Gingles, Ruth Symon, Stephen J Gandy, Allan D Struthers, Graeme Houston, Thomas M MacDonald, Chim C Lang, Peter T Donnan, Jacob George, Christopher R Gingles, Ruth Symon, Stephen J Gandy, Allan D Struthers, Graeme Houston, Thomas M MacDonald, Chim C Lang, Peter T Donnan, Jacob George

Abstract

Objectives: Previous studies have demonstrated that high-dose allopurinol is able to regress left ventricular (LV) mass in cohorts with established cardiovascular disease. The aim of this study was to assess whether treatment with high-dose allopurinol would regress LV mass in a cohort with essential hypertension, LV hypertrophy and well-controlled blood pressure but without established cardiovascular disease.

Methods: We conducted a mechanistic proof-of-concept randomized, placebo-controlled, double-blind trial of allopurinol (600 mg/day) versus placebo on LV mass regression. Duration of treatment was 12 months. LV mass regression was assessed by Cardiac Magnetic Resonance. Secondary outcomes were changes in endothelial function (flow-mediated dilatation), arterial stiffness (pulse wave velocity) and biomarkers of oxidative stress.

Results: Seventy-two patients were randomized into the trial. Mean baseline urate was 362.2 ± 96.7 μmol/l. Despite good blood pressure control, LV mass regression was significantly reduced in the allopurinol cohort compared with placebo (LV mass -0.37 ± 6.08 versus -3.75 ± 3.89 g; P = 0.012). Oxidative stress markers (thiobarbituric acid reactive substances) were significantly higher in the allopurinol group versus placebo (0.26 ± 0.85 versus -0.34 ± 0.83 μmol/l; P = 0.007). Other markers of vascular function were not significantly different between the two groups.

Conclusion: Treatment with high-dose allopurinol in normouricemic controlled hypertensive patients and LV hypertrophy is detrimental. It results in reduced LV mass regression and increased oxidative stress over a 12-month period. This may be because of an adverse impact on redox balance. Cohort selection for future cardiovascular trials with allopurinol is crucial.

Trial registration: ClinicalTrials.gov NCT02237339.

Figures

FIGURE 1
FIGURE 1
Study visits.
FIGURE 2
FIGURE 2
Consort diagram.
FIGURE 3
FIGURE 3
(a) The effect of allopurinol on left ventricular mass index (height1.7). Data expressed as mean ± SD. (b) The effect of allopurinol on left ventricular mass.

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